ANTIBODIES AS TOOLS IN CARDIOVASCULAR RESEARCH

我们对抗体结构和功能的认识的演变 合并站点已经发展到现在可以现实地 考虑将抗体作为引人注目的试剂或药物的应用 专一性。与传统药物不同的是，传统药物是一种有机小分子 这允许与其目标部位，即抗体进行有限的接触 结合点相对宽敞。这允许大量的原子间相互作用 与配体接触，允许显著的选择性以及非常高的 亲和力。产生抗体的细胞融合方法的研究进展 允许产生具有明确特异性的同种抗体 可复制的方式。在拟议的计划中，抗体结合部位将 被调查为心血管研究的主要工具。在最基本的情况下 水平，将解剖地高辛特异性抗体的结合部位。 就其一级结构而言，抗体适合于 治疗用途可以通过化学合成产生，或者替代地通过 翻译是一种基因信息。再次利用地高辛特异性抗体作为 模型中，将检查抗体片段的药理作用 临床研究中的特性。所允许的分子性质的分辨率 由于抗体结合部位的特异性，将对其加以利用 在对肾素的生理、病理生理学和生物合成的解剖中； 对肾上腺素能受体的性质和纯化的认识 抗体；以及在阐明前列腺素和 血管紧张素受体。所有这些项目的调查人员都有一个共同的 研究工具抗体结合部位和联合利用设施 蛋白质化学和细胞融合实验室的生产和理解 他们使用的试剂。

The evolution of our understanding of the structure and function of the antibody combining site has advanced to the point that one can now realistically contemplate the application of antibodies as reagents or drugs of remarkable specificity. Unlike the conventional drug, which is a small organic molecule that allows a limited number of contacts with its target site, the antibody combining site is relatively capacious. This permits numerous interatomic contacts with a ligand, allowing for remarkable selectivity as well as very high affinity. The development of cell fusion methods for producing antibodies now permits the production of homogeneous antibodies of defined specificity in a reproducible manner. In the proposed program, the antibody combining site will be investigated as a major tool in cardiovascular research. On a most basic level, the combining site of antibodies specific for digoxin will be dissected with respect to its primary structure so that antibodies suitable for therapeutic use might be produced by chemical synthesis or alternatively by translation a gene message. Again utilizing digoxin specific antibody as a model, antibody fragments will be examined with respect to their pharmacologic properties in clinical studies. The resolution of molecular properties allowed by the specificity of the antibody combining site will be utilized to advantage in the dissection of the physiology, pathophysiology, and biosynthesis of renin; in the understanding of the properties and purification of adrenergic receptor antibodies; and in the elucidation of the function of prostaglandin and angiotensin receptors. The investigators in all these projects have as a common research tool the antibody combining site and utilize conjointly the facilities of a protein chemistry and cell fusion laboratory to produce and understand the reagents that they utilize.